MicroRNA-Dependent Targeting of RSU1 and the IPP Adhesion Complex Regulates the PTEN/PI3K/AKT Signaling Pathway in Breast Cancer Cell Lines

Kim, Yong-Chul; Cutler, Mary Lou

doi:10.3390/ijms21155458

Cited by 3 publications

(2 citation statements)

References 80 publications

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“…Our study also con rmed the connection between signals in recipient cells and mediators within exosomes. Previous studies have demonstrated that the effects of miR-221-3p were mediated via increasing Akt kinase activity and inhibiting PTEN [59,60]. In agreement with these ndings, our results showed that the inhibitors of miR-221-3p attenuated enhanced expression of PTEN and p-Akt induced by hucMSC-Exos.…”

Section: Discussionsupporting

confidence: 92%

Exosomes from Human Umbilical Cord Mesenchymal Stem Cells Facilitate Diabetic Wound Healing through miR-221-3p-mediated Enhancement of Angiogenesis

Wei

Wang

et al. 2021

Preprint

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Background: Endothelial dysfunction caused by persistent hyperglycemia in diabetes is responsible for impaired angiogenesis in diabetic wounds. Exosomes are considered potential therapeutic tools to promote diabetic wound healing. The aim of this study was to investigate the effects of exosomes secreted by human umbilical cord mesenchymal stem cells (hucMSC-Exos) on angiogenesis under high glucose (HG) conditions in vivo and in vitro and to explore the underlying mechanisms.Methods: HucMSC-Exos were used to treat diabetic wounds and human umbilical vascular endothelial cells (HUVECs) exposed to HG. Wound healing and angiogenesis were assessed in vivo. The biological characteristics of HUVECs were examined in vitro. Expression of pro-angiogenesis genes in HUVECs was also examined by western blotting. The miRNAs contained within hucMSC-Exos were identified using miRNA microarrays and qRT-PCR. The roles of selected miRNAs in angiogenesis were assessed using specific agomirs and inhibitors.Results: In vivo, local application of hucMSC-Exos enhanced wound healing and angiogenesis. In vitro, hucMSC-Exos reduced senescence of HG-treated HUVECs and promoted proliferation, migration, and tube formation by inhibiting phosphatase and tensin homolog (PTEN) expression and activating the AKT/HIF-1α/VEGF pathways. MiR-221-3p was enriched in hucMSC-Exos. In vitro, MiR-221-3p downregulated PTEN and activated the AKT/HIF-1α/VEGF pathway to promote proliferation, migration, and tube formation in HG-treated HUVECs. In vivo, miR-221-3p agomirs mimicked the effects of hucMSC-Exos on wound healing and angiogenesis, whereas miR-221-3p inhibitors reversed their effects.Conclusions: Our findings suggest that hucMSC-Exos have regenerative and protective effects on HG-induced senescence in endothelial cells via transfer of miR-221-3p, thereby accelerating diabetic wound healing. Thus, hucMSC-Exos may be promising therapeutic candidates for improving diabetic wound angiogenesis.

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Section: Discussionsupporting

confidence: 92%

Exosomes from Human Umbilical Cord Mesenchymal Stem Cells Facilitate Diabetic Wound Healing through miR-221-3p-mediated Enhancement of Angiogenesis

Wei

Wang

et al. 2021

Preprint

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“…In order to evaluate the expression of several miRNAs that have been reported as related to BCa development and progression [ 11 , 12 , 13 , 14 , 15 ], we developed a triple negative BCa (TNBC) mice model. Balb/c animals were randomly divided into two groups (BCa or control) and inoculated or not with 4T1 cells.…”

Section: Resultsmentioning

confidence: 99%

MiR-106b-5p: A Master Regulator of Potential Biomarkers for Breast Cancer Aggressiveness and Prognosis

Farré

Duca

Massillo

et al. 2021

IJMS

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Breast cancer (BCa) is the leading cause of death by cancer in women worldwide. This disease is mainly stratified in four subtypes according to the presence of specific receptors, which is important for BCa aggressiveness, progression and prognosis. MicroRNAs (miRNAs) are small non-coding RNAs that have the capability to modulate several genes. Our aim was to identify a miRNA signature deregulated in preclinical and clinical BCa models for potential biomarker discovery that would be useful for BCa diagnosis and/or prognosis. We identified hsa-miR-21-5p and miR-106b-5p as up-regulated and hsa-miR-205-5p and miR-143-3p as down-regulated in BCa compared to normal breast or normal adjacent (NAT) tissues. We established 51 shared target genes between hsa-miR-21-5p and miR-106b-5p, which negatively correlated with the miRNA expression. Furthermore, we assessed the pathways in which these genes were involved and selected 12 that were associated with cancer and metabolism. Additionally, GAB1, GNG12, HBP1, MEF2A, PAFAH1B1, PPP1R3B, RPS6KA3 and SESN1 were downregulated in BCa compared to NAT. Interestingly, hsa-miR-106b-5p was up-regulated, while GAB1, GNG12, HBP1 and SESN1 were downregulated in aggressive subtypes. Finally, patients with high levels of hsa-miR-106b-5 and low levels of the abovementioned genes had worse relapse free survival and worse overall survival, except for GAB1.

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Emerging roles of activating transcription factor 2 in the development of breast cancer: a comprehensive review

Amarah,

Elsabagh,

Ouda

et al. 2023

Precision Clinical Medicine

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Activating transcription factor 2 (ATF2) is a member of the leucine zipper family of DNA binding proteins that are responsible for regulating various genes that play an essential role in major biological and cellular functions. Since ATF2 plays a vital role in cellular proliferation and apoptosis, it is believed that it greatly affects the development of breast cancers. However, its exact role in breast cancer is incompletely understood. It remains a subject of debate, ambiguity, and continuous research. Several studies have suggested the role of ATF2 as an oncogene, promoting cellular proliferation and worsening the outcome of cancers. In contrast, other studies have postulated that ATF2 plays a tumor suppressive role in estrogen receptor-positive breast cancer. The ambiguity surrounding its role in breast cancer is the reason why there is an influx of recent studies and research in this area. In this narrative review, we investigate several studies that have been published about the role of ATF2 in breast cancer. We also explored studies that have examined the association between ATF2 and endocrine therapy resistance. ATF2 has been suggested to modulate ER expression and activity, potentially affecting tamoxifen sensitivity in breast cancer cells. Therefore, the role of ATF2 in DNA repair mechanisms and drug resistance has been deeply explored in this review. Additionally, there are numerous ongoing clinical trials exploring the effect of targeting ATF2 pathways and mechanisms on the outcome of breast cancers, some of which we have discussed. The previous studies and clinical trials that are being conducted to understand the multifaceted role of ATF2 and its signaling pathways may provide valuable insight for developing efficient targeted therapeutic solutions to enhance the outcomes of breast cancer and overcome endocrine resistance. We warrant further research to elucidate the dual roles of ATF2 in breast cancer and potential therapeutic therapies for its treatment.

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MicroRNA-Dependent Targeting of RSU1 and the IPP Adhesion Complex Regulates the PTEN/PI3K/AKT Signaling Pathway in Breast Cancer Cell Lines

Cited by 3 publications

References 80 publications

Exosomes from Human Umbilical Cord Mesenchymal Stem Cells Facilitate Diabetic Wound Healing through miR-221-3p-mediated Enhancement of Angiogenesis

Exosomes from Human Umbilical Cord Mesenchymal Stem Cells Facilitate Diabetic Wound Healing through miR-221-3p-mediated Enhancement of Angiogenesis

MiR-106b-5p: A Master Regulator of Potential Biomarkers for Breast Cancer Aggressiveness and Prognosis

Emerging roles of activating transcription factor 2 in the development of breast cancer: a comprehensive review

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